Conclusion
Our data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.

Doesn't the Silverman / Klein paper get us closer to a piciture of just how XMRV can be a true pathogen? I think it may represent something of a breakthrough study, small though it is. I feel a bit cheered! "suggests a profound effect of the virus on fundamental cellular physiology and inflammation. These findings could be relevant to the possible pathogenic effects on [sic--for "of"] XMRV in prostate cancer." OK, not yet CFS, and "could be," "possible," but.. Chris

This is one of the enticing things about XMRV. Dusty Miller has data on its effects on nerve cells, it may be found in B cells - which may be a key source of mischief in CFS...and now this study shows that if you infect a cell line with it that cell line triggers activity in the gene associated with a major, major player in inflammation...

INTRODUCTION AND OBJECTIVES
XMRV is a novel human retrovirus associated with prostate cancer. Although other gammaretroviruses cause cancer in animals, it remains unknown if XMRV is a cause of disease. However, indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. To gain insight into the possible role of XMRV in these diseases we have identified genes that are induced in response to XMRV infection.

Back to Article Outline

METHODS
Prostate cancer cell line DU145 was infected for 8, 24, 48 and 120h with XMRV. A comparison to uninfected DU145 cells cultured for the same periods of time served as controls. A population of total RNA was isolated using Qiagen RNeasy Mini Kit followed by digestion of DNA with DNAse treatment. XMRV infections at the different time points were monitored using real-time RT-PCR for env XMRV RNA. The RNA samples were analyzed for gene expression using Sentrix humanRef-8 v3 expression bead chips from Illumina (Cleveland Clinic Genomics Core). To verify the results obtained by the array experiment, we determined induction of a subset of the regulated genes. Total RNA was reverse transcribed to cDNA using iScript Select cDNA Synthesis Kit from Bio-Rad (random primers method). Induction of selected genes by XMRV infection was verified by qPCR (Relative Quantification) from the cDNA pool using SYBR Green master mix. Fold-induction at each time point for the individual mRNAs was determined. In addition, pathway predictions were determined using Ingenuity Systems (content version 3002) software for genes induced by more than 2-fold following XMRV infection.

The chemokine IL-8 is one of the most highly induced genes in response to XMRV infection of prostate cancer cell line DU145. XMRV induction of the 30 host genes identified in this study suggests a profound effect of the virus on fundamental cellular physiology and inflammation. These findings could be relevant to the possible pathogenic effects on XMRV in prostate cancer.

Conclusion
Our data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.

Click to expand...

Crazy, huh... I can't believe this is a coincidence anymore. Maybe it would be interesting to find out a bit more about who makes the decisions at Retrovirology, who owns it etc. I wonder what will happen with Retrovirology in case XMRV were to be confirmed as an infectious virus present in the population. Will they close? Change the name??

This is one of the enticing things about XMRV. Dusty Miller has data on its effects on nerve cells, it may be found in B cells - which may be a key source of mischief in CFS...and now this study shows that if you infect a cell line with it that cell line triggers activity in the gene associated with a major, major player in inflammation...

Click to expand...

It's almost cruel. Wasn't there work showing XMRV reacting with EBV?

There are so many things about XMRV which make it seem plausible as a cause for CFS. Other than the growing evidence that there's no correlation and it's all just contamination! Hopefully we'll hear something solid, one way or the other, from the BWG or Lipkin soon.

Doesn't the Silverman / Klein paper get us closer to a piciture of just how XMRV can be a true pathogen? I think it may represent something of a breakthrough study, small though it is. I feel a bit cheered! "suggests a profound effect of the virus on fundamental cellular physiology and inflammation. These findings could be relevant to the possible pathogenic effects on [sic--for "of"] XMRV in prostate cancer." OK, not yet CFS, and "could be," "possible," but.. Chris

Click to expand...

I think so. I'm no scientist, so i might be wrong, but i feel that with the evidence we have up to now, it's more or less clear that XMRV really is a virus capable of infecting a host and the positive findings could not be explained by contamination with any sort of mouse material. And the virus seems to have some effects on the host, so it seems to be a serious thing, regardless of where it arose or wheter there is an association with ME/CFS or not. So i think there should be an interest to get to the bottom of it anyway, especially with people working in labs and there will be more studies.

Of course this study was probably submitted quite some time before the CROI, so we can't know for sure how Silverman and Klein feel about things now. But the fact that the journal still published those studies seems to indicate that they don't think it's clear that all the positive findings in humans are explained by contamination.

Does anyone know who is in control after the submission of a paper? Would the authors have the right to withdraw the paper?

Is there any way the US government could prevent the publication of a paper that does not contain any illegal content by a privately owned journal? They would need a law that allows them to do that, at least under the constitutions i know about. Maybe there's a law that would allow for that if the paper would pose a danger to national security or something like that...

I think any one of, the authors, the journal, or the gov't, could each have withdrawn the paper.

Click to expand...

Yes, typically the authors (or their organizations) or the journal can withdraw a paper. If the latest research clearly made the paper obsolete/incorrect that would probably (not certainly) have been done.

Is there any way the US government could prevent the publication of a paper that does not contain any illegal content by a privately owned journal? They would need a law that allows them to do that, at least under the constitutions i know about. Maybe there's a law that would allow for that if the paper would pose a danger to national security or something like that...

Click to expand...

I don't think so. However, significant pressure can probably be brought to bear on the journal in question, so while the gov't may not be able to absolutely prohibit it, it may be able to effectively prevent publication.

ConclusionOur data show no solid evidence of XMRV infection in any of the three populations tested, implying that there is no association between the onset of PC or CFS and XMRV infection in Japan. However, the lack of adequate human specimens as a positive control in Ab screening and the limited sample size do not allow us to draw a firm conclusion.

Click to expand...

While I'm no fan of Retrovirology, this paper does not disturb me as much as others have. This is a properly written conclusion. The parts I bolded show that they understand and clearly state the limits of their research, and their conclusion does not extrapolate beyond the data.

I have no problem with a paper that looks for XMRV infection and doesn't find it as long as they clearly identify their sample set and methodology and keep their conclusions within the bounds of their data. Plenty of labs are not going to find XMRV -- possibly because it isn't there, or their sample set is not good, or their methodology doesn't work, or a number of other reasons. That's to be expected. It helps us clarify the limits that exist for finding XMRV.

It's the garbage that uses a terrible sample set and unproven methods, and then conclude that because they didn't find it with their method it isn't there that bother me. Honestly. I wouldn't accept that from an undergraduate. Maybe medical research is much sloppier with scientific rigor, but I hope not.

Of course this study was probably submitted quite some time before the CROI, so we can't know for sure how Silverman and Klein feel about things now. But the fact that the journal still published those studies seems to indicate that they don't think it's clear that all the positive findings in humans are explained by contamination.

Does anyone know who is in control after the submission of a paper? Would the authors have the right to withdraw the paper?

Click to expand...

I realldy doubt that Silverman and Klein think XMRV is all contamination. So they had 22RV1 in a freezer in their laboratory - but did it infect samples taken for the WPI, NCI, Singh's study, Germans, Japanese, De-Meileir study, clinical samples checked by VIP Dx and RED Labs, samples checked at the IrisCaixa in spain etc etc etc? Most of these did not work with 22RV1 ever.